Despite preventative measures, traumatic brain injury (TBI) remains the leading cause of death and disability in children. While most pediatric treatment regimens for TBI to date are derived from adult studies, no therapeutic regimen has been particularly successful in improving outcome in children. There have been numerous laboratory studies utilizing moderate hypothermia (HYPO) (32-33[unreadable]C) in mature and immature animals, successful Phase II and III clinical studies in adult patients for 24 to 48 h after TBI, and a number of trials in children of HYPO following hypoxia-ischemic (HIE) brain injuries that have supported the efficacy of this intervention. The most recently published trial of treatment with HYPO for HIE within 6 hours showed significant improvement in outcome, particularly in mortality, as compared to severe disability. While the multi-center Phase III randomized controlled clinical trial (RCT) of moderate HYPO in adults was stopped early due to futility but not lack of efficacy, the secondary analysis did highlight that younger adult patients (< 40 y) tended toward improved outcome compared to older subjects. This finding along with a trend toward improved outcomes with early cooling (< 6 h) has resulted in a funded HYPO RCT specifically inclusive of patients ages 16- 45 y and early pre-hospital cooling that has recently begun. Based on the results from our Pilot Clinical Trial (PCT) utilizing moderate HYPO following severe TBI in children, the following application is for a multicenter Phase III RCT to determine whether induced early cooling (within 6 h) (32-33[unreadable]C) after severe TBI in children and maintained for 48 h will improve mortality at 3 mos post injury as compared to normothermia (37- 38[unreadable]C). The Secondary Hypotheses, again based on the analysis of the PCT, are that early HYPO after severe TBI in children and maintained for 48 h: 1) will improve global function as measured by the GOS/ GOS- Extended Pediatrics (GOS- E Peds) and neurocognitive status across the domains of intellectual development, learning and memory, and behavior at 6 and 12 mos after injury; 2) will be more effective in younger children < 6 y compared to older children, > 6y, and 3) will lessen intracranial hypertension and the intensity of therapy necessary for control of ICP. [unreadable] [unreadable] [unreadable]